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Abstract Cardiovascular disease (CVD) is the leading cause of mortality, disability, and healthcare costs, with a significant impact on the elderly and contributing to premature deaths across various age groups, including those below age 70. Despite decades of transformative discoveries and clinical efforts, the challenges of diagnosis, prevention, and treatment of CVD persist on a massive scale. This study aimed to unravel potential CVD-associated biomarkers and establish a machine learning model for the risk assessment of CVD. Untargeted metabolic assay with ultra-high performance liquid chromatography-tandem mass spectrometry and routine clinical biochemistry test were undertaken on the fasting venous blood specimens from 57 subjects. Four relevant clinical traits and 164 CVD-associated metabolites were identified, especially those related to glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. The machine learning model achieved from an integrated biomarker panel of palmitic amide, oleic acid, 138-pos (the 138th detected metabolomic feature in positive ion mode), phosphatidylcholine, linoleic acid, age, direct bilirubin, and inorganic phosphate, was able to improve the accuracy of CVD risk assessment up to a high satisfactory value of 0.91. The findings indicate that disorders in the metabolic processes of biological membranes and energy are significantly associated with increased risk of vascular damage in CVD patients. With machine learning methods, the pivotal metabolites and clinical biomarkers offer a promising potential for the efficient risk assessment and diagnosis of CVD.

Excessive carbon emissions and the destruction of vegetation caused by human activities threaten the carbon balance and ecosystem security. Carbon sequestration flow (CSF) becomes a necessary carbon exchange between socio-ecological systems. Thus, assessing the utility of carbon sequestration (CS) based on CSF is crucial for adaptive management. We establish a process-oriented CSF model and evaluate the utility of CS around self-sufficiency, cross-regional synergy, and ecological carrying capacity to explore ecological development models. The findings indicate that CS supply is satisfactory, but demand for CS is increasing. The western section of the Qinling mountains exhibits high self-sufficiency and ecological carrying capacity but poor cross-regional synergy. The central region has moderate self-sufficiency and favorable cross-regional synergy and faces threats to ecological carrying capacity. Henan faces lower self-sufficiency and cross-regional synergy, and the ecological carrying capacity is loaded. Furthermore, we propose adaptive strategies for ecological development models that are significant for ecological zoning management.

Abstract Background The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. Results We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). Conclusions Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy. Graphical abstract

Alpine marginal ecosystems above the natural tree line are considered to be the most vulnerable habitats for maintaining local biodiversity. The soil microbial community is crucial for ecosystem stability and function. However, our comprehension of the overall soil microbial community in alpine marginal ecosystems remains limited, particularly regarding environmental stress. We selected the Baima Mountain National Nature Reserve (BMNNR) in the northwest Yunnan provinces as our study area and collected soil samples from three different depth layers, in alpine marginal ecosystems. The phospholipid fatty acid (PLFA) analysis method was utilized to evaluate alterations in soil microbial communities. The results showed that: (1) the PLFA content gradually decreased with increasing soil depth; (2) on the whole, the variations in PLFA across alpine marginal ecosystems were obviously, the highest in alpine meadow (AM) and the lowest in alpine screes (AS); (3) the site effect exerted a greater direct influence than microhabitat effect and elevation (0–5 cm, 32 %, 16 % and 9 %, respectively; 20–40 cm, 46 %, 29 % and 0 %, respectively), with the direct impact of elevation decreasing as soil depth increased (0–5 cm, 5–20 cm and20-40 cm, 9 %, 1 % and 0 %, respectively); and (4) the ratio of cyclopropyl to precursors (Cy:Pre) in all communities was > 0.1, indicating that the soil microbial community was under environmental stress. This study demonstrates the potential of PLFA analysis to profile soil microbial communities and their stress status under field conditions and also provides a better understanding of the correlation between soil microbial communities and the function and health of alpine marginal ecosystems.

Abstract Treatment of sensitive bacteria with beta‐lactam antibiotics often leads to two salient population‐level features: a transient increase in total population biomass before a subsequent decline, and a linear correlation between growth and killing rates. However, it remains unclear how these population‐level responses emerge from collective single‐cell responses. During beta‐lactam treatment, it is well‐recognized that individual cells often exhibit varying degrees of filamentation before lysis. We show that the cumulative probability of cell lysis increases sigmoidally with the extent of filamentation and that this dependence is characterized by unique parameters that are specific to bacterial strain, antibiotic dose, and growth condition. Modeling demonstrates how the single‐cell lysis probabilities can give rise to population‐level biomass dynamics, which were experimentally validated. This mapping provides insights into how the population biomass time‐kill curve emerges from single cells and allows the representation of both single‐ and population‐level responses with universal parameters.

Abstract Glioma is the most common malignant tumor of the central nervous system in adults. The tumor microenvironment (TME) is related to poor prognosis in glioma patients. Glioma cells could sort miRNA into exosomes to modify TME. And hypoxia played an important role in this sorting process, but the mechanism is not clear yet. Our study was to find miRNAs sorted into glioma exosomes and reveal the sorting process. Sequencing analysis of glioma patients cerebrospinal fluid (CSF) and tissue showed that miR-204-3p tends to be sorted into exosomes. miR-204-3p suppressed glioma proliferation through the CACNA1C/MAPK pathway. hnRNP A2/B1 can accelerate exosome sorting of miR-204-3p by binding a specific sequence. Hypoxia plays an important role in exosome sorting of miR-204-3p. Hypoxia can upregulate miR-204-3p by upregulating the translation factor SOX9. Hypoxia promotes the transfer of hnRNP A2/B1 to the cytoplasm by upregulating SUMOylation of hnRNP A2/B1 to eliminate miR-204-3p. Exosomal miR-204-3p promoted tube formation of vascular endothelial cells through the ATXN1/STAT3 pathway. The SUMOylation inhibitor TAK-981 can inhibit the exosome-sorting process of miR-204-3p to inhibit tumor growth and angiogenesis. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma.

Abstract Background Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been systematically performed. Methods We performed a comprehensive analysis of TMSs and thymosin β10 (TMSB10) using multiomics data from more than 10,000 tumor samples of 33 cancer types from The Cancer Genome Atlas (TCGA). We used single-sample gene set enrichment analysis (ssGSEA) and the gene set variation analysis (GSVA) algorithm to investigate the differences in tumor microenvironment (TME) cell infiltration and functional annotation for individual tumor samples, respectively. The role of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration,and immunosuppressive polarization, and the combination drug efficacy were assessed via biological function assays. Results We comprehensively assessed genomic mutations, expression dysregulation, prognosis and immunotherapeutic response across 33 human cancer samples and showed that TMSB10 is specifically overexpressed in almost all types of cancer tissues. Further pan-cancer analysis showed that TMSB10 is closely related to the biological function, immune regulation and prognosis of glioma. Similar results were also found in several public glioma cohorts and our Qilu local cohort. Further integration with other biological experiments revealed the key roles of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration and immunosuppressive polarization. We also identified multiple drugs targeting cells with high TMSB10 expression and validated that knockdown of TMSB10 improved the efficacy of selumetinib (a MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis-associated tumors) and anti-PD1 treatment in glioma. Conclusion These results indicate that TMSB10 holds promise as a novel prognostic marker and therapeutic target, providing a theoretical basis for the development of more effective and targeted clinical treatment strategies for glioma patients.

Abstract Osteoarthritis, a chronic degenerative cartilage disease, is the leading cause of movement disorders among humans. Although the specific pathogenesis and associated mechanisms remain unclear, oxidative stress‐induced metabolic imbalance in chondrocytes plays a crucial role in the occurrence and development of osteoarthritis. In this study, a trimanganese tetroxide (Mn3O4) nanozyme with superoxide dismutase (SOD)‐like and catalase (CAT)‐like activities is designed to reduce oxidative stress‐induced damage and its therapeutic effect is investigated. In vitro, Mn3O4 nanozymes are confirmed to reprogram both the imbalance of metabolism in chondrocytes and the uncontrolled inflammatory response stimulated by hydrogen peroxide. In vivo, a cross‐linked chondroitin sulfate (CS) hydrogel is designed as a substrate for Mn3O4 nanozymes to treat osteoarthritis in mouse models. As a result, even in the early stage of OA (4 weeks), the therapeutic effect of the Mn3O4@CS hydrogel is observed in both cartilage metabolism and inflammation. Moreover, the Mn3O4@CS hydrogel maintained its therapeutic effects for at least 7 days, thus revealing a broad scope for future clinical applications. In conclusion, these results suggest that the Mn3O4@CS hydrogel is a potentially effective therapeutic treatment for osteoarthritis, and a novel therapeutic strategy for osteoarthritis based on nanozymes is proposed.

Abstract Clear evidence shows that tumors could secrete microRNAs (miRNAs) via exosomes to modulate the tumor microenvironment (TME). However, the mechanisms sorting specific miRNAs into exosomes are still unclear. In order to study the biological function and characterization of exosomal miRNAs, we performed whole-transcriptome sequencing in 59 patients’ whole-course cerebrospinal fluid (CSF) small extracellular vesicles (sEV) and matched glioma tissue samples. The results demonstrate that miRNAs could be divided into exosome-enriched miRNAs (ExomiRNAs) and intracellular-retained miRNAs (CLmiRNAs), and exosome-enriched miRNAs generally play a dual role. Among them, miR-1298-5p was enriched in CSF exosomes and suppressed glioma progression in vitro and vivo experiments. Interestingly, exosomal miR-1298-5p could promote the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) to facilitate glioma. Therefore, we found miR-1298-5p had different effects on glioma cells and MDSCs. Mechanically, downstream signaling pathway analyses showed that miR-1298-5p plays distinct roles in glioma cells and MDSCs via targeting SETD7 and MSH2, respectively. Moreover, reverse verification was performed on the intracellular-retained miRNA miR-9-5p. Thus, we confirmed that tumor-suppressive miRNAs in glioma cells could be eliminated through exosomes and target tumor-associated immune cells to induce tumor-promoting phenotypes. Glioma could get double benefit from it. These findings uncover the mechanisms that glioma selectively sorts miRNAs into exosomes and modulates tumor immunity.

As one of the most common post-transcriptional modifications of mRNAs and noncoding RNAs, N6-methyladenosine (m6A) modification regulates almost every aspect of RNA metabolism. Evidence indicates that dysregulation of m6A modification and associated proteins contributes to glioblastoma (GBM) progression. However, the function of fat mass and obesity-associated protein (FTO), an m6A demethylase, has not been systematically and comprehensively explored in GBM. Here, we found that decreased FTO expression in clinical specimens correlated with higher glioma grades and poorer clinical outcomes. Functionally, FTO inhibited growth and invasion in GBM cells in vitro and in vivo. Mechanistically, FTO regulated the m6A modification of primary microRNA-10a (pri-miR-10a), which could be recognized by reader HNRNPA2B1, recruiting the microRNA microprocessor complex protein DGCR8 and mediating pri-miR-10a processing. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor SPI1, which could be specifically disrupted by the SPI1 inhibitor DB2313. Treatment with this inhibitor restored endogenous FTO expression and decreased GBM tumor burden, suggesting that FTO may serve as a novel prognostic indicator and therapeutic molecular target of GBM.

Summary: Cuproptosis is a novel form of cell death driven by a copper-dependent proteotoxic stress response whose comprehensive landscape in tumors remains unclear. Here, we comprehensively characterized cuproptosis-related genes (CRGs) across 33 cancers using multi-omic data from The Cancer Genome Atlas (TCGA), showing complicated and diverse results in different cancers. We also explored the relationships between CRGs and cancer metabolic patterns, pathway activity, and tumor microenvironment (TME), suggesting that they played critical roles in tumor progression and TME cell infiltration. We further established the cuproptosis potential index (CPI) to reveal the functional roles of cuproptosis, and characterized multi-omic molecular features associated with cuproptosis. In clinical applications, we performed a combined analysis of the sensitivity of CRGs and CPI to drug response and immunotherapy. This study provides a rich resource for understanding cuproptosis, offering a broad molecular perspective for future functional and therapeutic studies of multiple cancer pathways mediated by cuproptosis.

A newly identified form of cell death known as ferroptosis is characterized by the peroxidation of lipids in response to iron. Rapid progress in research on ferroptosis in glioma and neuroblastoma has promoted the exploitation of ferroptosis in related therapy. This manuscript provides a review of the findings on ferroptosis-related therapy in glioblastoma and neuroblastoma and outlines the mechanisms involved in ferroptosis in glioma and neuroblastoma. We summarize some recent data on traditional drugs, natural compounds and nanomedicines used as ferroptosis inducers in glioma and neuroblastoma, as well as some bioinformatic analyses of genes involved in ferroptosis. Moreover, we summarize some data on the associations of ferroptosis with the tumor immunotherapy and TMZ drug resistance. Finally, we discuss future directions for ferroptosis research in glioma and neuroblastoma and currently unresolved issues.

Abstract Background Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. Methods CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. Results We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. Conclusions This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.

Long-term vegetation dynamics with satellite observations can provide valuable insights into natural variation in ecosystems and quantify disturbances associated with external pressures. Monitoring vegetation dynamics within protected areas (PAs) is essential, given their crucial role in protecting biodiversity and maintaining ecosystem integrity. In this study, using the normalized difference vegetation index (NDVI) and Breaks For Additive Seasonal and Trend (BFAST)model, we detected vegetation dynamics especially abrupt changes inside nature reserves (NRs, the primary type of PAs) on the Qinghai-Tibetan Plateau from 2000 to 2020. We then applied the matching approach and postmatching regression to evaluate the effect of NRs on natural vegetation with average NDVI, NDVI slope, and the number of abrupt changes. Our results showed that 78.97% of the vegetation within NRs exhibited greening trends. In addition, 29.15% of the area inside of the NRs experienced 1 or more abrupt changes, with the major change type interrupted greening (15.96%), followed by greening to browning (6.27%) and browning to greening (4.00%). The NRs significantly reduced the frequency of disturbances, and older NRs also showed a higher value of average NDVI compared to those in matched unprotected areas. Postregression models indicated that vegetation in newer NRs tended to be more vulnerable to disturbances and stricter NR management could benefit vegetation enhancement. Our analysis offers a new approach to vegetation dynamic monitoring that considers short-term disturbances. The findings of this work can help better understand effectiveness of PAs on ecosystem protection and offer practical guidance to future PAs management.

Foundation settlement prediction is significant to the reuse and management of the reclaimed land from the sea by dykes where composite stratum of many strata with different physical and mechanical properties is encountered. Toward the foundation settlement analysis of reclaimed land in the Yellow Sea composite stratum in eastern China, a weighted-combination model is proposed in this paper combining the hyperbolic model, exponential curve model, and Asaoka model. First, the weight coefficient of the weighted-combination model is calculated by the reciprocal square method of average absolute error (MAE). Second, the settlement prediction results of different models are evaluated by the absolute error, MAE, root-mean-square error, and mean absolute percentage error. Finally, the settlement mechanism of reclaimed foundations in a composite stratum is analyzed from the point of view of the multistratum coupling, and the adaptability of different models to the settlement prediction of reclaimed foundations in a composite stratum is discussed. The results show that the predicted settlement duration curves of the weighted-combined model are in good agreement with the measured settlement duration curves, and the prediction performance is better than that of the hyperbolic model, exponential curve model, and Asaoka model. The MAE of the weighted-combination model is 75.7% lower than that of the exponential curve model, 90.2% lower than that of the hyperbolic model, and 70% lower than that of the Asaoka model. This model provides a new way to predict the settlement of reclaimed foundations in a similar composite stratum.

Abstract Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

Abstract Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis is a newly discovered method of programmed cell death and opens a new direction for GBM treatment. However, poor blood–brain barrier (BBB) penetration, reduced tumor targeting ability, and potential compensatory mechanisms hinder the effectiveness of ferroptosis agents during GBM treatment. Here, a novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the BBB penetration abilities and siRNA encapsulation properties of engineered exosomes for GBM therapy is presented. This platform can be enriched in the brain under local magnetic localization and angiopep‐2 peptide‐modified engineered exosomes can trigger transcytosis, allowing the particles to cross the BBB and target GBM cells by recognizing the LRP‐1 receptor. Synergistic ferroptosis therapy of GBM is achieved by the combined triple actions of the disintegration of dihydroorotate dehydrogenase and the glutathione peroxidase 4 ferroptosis defense axis with Fe3O4 nanoparticle‐mediated Fe2+ release. Thus, the present findings show that this system can serve as a promising platform for the treatment of glioblastoma.

Adipose-derived stem cells (ADSCs) treatment offers support to new methods of transporting baseline cell protein endothelial cells in alginate (A)/silk sericin (SS) lamellar-coated antioxidant system (ASS@L) to promote acute myocardial infarction. In the synthesized frames of ASS, the ratio of fixity modules, pores, the absorption and inflammation was detected at ka (65ka), 151 ± 40.12 μm, 92.8%, 43.2 ± 2.58 and 30.10 ± 2.1. In this context, ADSC-ASS@L was developed and the corresponding material was stable and physically chemical for the development of cardiac regenerative applications. ADSC-ASS@L injectable hydrogels in vitro examination demonstrated higher cell survival rates and pro-angiogenic and pro-Inflammatory expression factors, demonstrating the favorable effect of fractional ejections, fibre-areas, and low infracture vessel densities. In successful cardiac damage therapy in acute myocardial infarction the innovative ADSC injection hydrogel approach may be helpful. The approach could also be effective during coronary artery hypertrophy for successful heart damage treatment.

BackgroundGlioblastoma (GBM) is a fatal brain tumor with no effective treatment. The specific GBM tumor immune microenvironment (TIME) may contribute to resistance to immunotherapy, a tumor therapy with great potential. Thus, an in-depth understanding of the characteristics of tumor-infiltrating immune cells is essential for exploring biomarkers in GBM pathogenesis and immunotherapy.MethodsWe estimated the relative abundances of 25 immune cell types in 796 GBM samples using single sample gene set enrichment analysis (ssGSEA). Unsupervised clustering was used to identify different GBM-associated TIME immune cell infiltration (GTMEI) patterns. The GTMEIscore system was constructed with principal component analysis (PCA) to determine the immune infiltration pattern of individual tumors.ResultsWe revealed three distinct GTMEI patterns with different clinical outcomes and modulated biological pathways. We developed a scoring system (GTMEIscore) to determine the immune infiltration pattern of individual tumors. We comprehensively analyzed the genomic characteristics, molecular subtypes and clinicopathological features as well as proteomic, phosphoproteomic, acetylomic, lipidomic and metabolomic properties associated with the GTMEIscore and revealed many novel dysregulated pathways and precise targets in GBM. Moreover, the GTMEIscore accurately quantified the immune status of many other cancer types. Clinically, the GTMEIscore was found to have significant potential therapeutic value for chemotherapy/radiotherapy, immune checkpoint inhibitor (ICI) therapy and targeted therapy.ConclusionsFor the first time, we employed a multilevel and multiplatform strategy to construct a multidimensional molecular map of tumors with different immune infiltration patterns. These results may provide theoretical basises for identifying more effective predictive biomarkers and developing more effective drug combination strategies or novel immunotherapeutic agents for GBM.

To understand the surface evolution in unsteady thermal environment of diesel engine, piston Al–Si–Cu alloy was ablated by a high frequent pulsing carburizing oxyacetylene combustion. The tested samples displayed good correlation with the characteristics of some bench tested pistons. As the loading cycles increased, the roughness slightly declined first and then rose sharply. Hardness evolution, micro-morphology, element and phase analysis suggested the surface roughness was mainly controlled by the thermal stress induced defects. And in combination with thermodynamics, the source of Al in surface deposited rimous carbon was ascertained to be chemical reactions between carburizing combustion and the Al–Si–Cu alloy.

A new image cryptosystem based on neuron-like scheme is proposed in this paper. As a non-linear component of image cryptosystem, neuron-like learning algorithm can realize a kind of memorable diffusion algorithm, thus realizing the plaintext-related image encryption algorithm. Through the feedback operation, the inputs and weights of the neuron are regulated by the information of the image, and then they are used to diffuse the image information. According to the needs of application scenarios, the number of inputs of the neuron can be adjusted so that the image cryptosystem can be applied to different security requirements. The simulation results show that the proposed image encryption system is extremely sensitive to the secret keys, the equivalent keys and the plain images, and also possesses the high security and adaptive characteristics. The image cryptosystem can be applied to the actual applications of image information security.

BackgroundGlioblastoma (GBM), one of the most aggressive tumors of the brain, has no effective or sufficient therapies. Identifying robust biomarkers for the response to immune checkpoint blockade (ICB) therapy, a promising treatment option for GBM patients, is urgently needed.MethodsWe comprehensively evaluated lncRNA m6A modification patterns in m6A-sequencing (m6A-seq) data for GBM tissues and systematically investigated the immune and stromal regulators of these m6A-regulated lncRNAs. We used the single-sample gene-set enrichment analysis (ssGSEA) algorithm to investigate the difference in enriched tumor microenvironment (TME) infiltrating cells and the functional annotation of HSPA7 in individual GBM samples. Further, we validated that HSPA7 promoted the recruitment of macrophages into GBM TME in vitro, as well as in our GBM tissue section. We also explored its impact on the efficacy of ICB therapy using the patient-derived glioblastoma organoid (GBO) model.ResultsHere, we depicted the first transcriptome-wide m6A methylation profile of lncRNAs in GBM, revealing highly distinct lncRNA m6A modification patterns compared to those in normal brain tissues. We identified the m6A-modified pseudogene HSPA7 as a novel prognostic risk factor in GBM patients, with crucial roles in immunophenotype determination, stromal activation, and carcinogenic pathway activation. We confirmed that HSPA7 promoted macrophage infiltration and SPP1 expression via upregulating the YAP1 and LOX expression of glioblastoma stem cells (GSCs) in vitro and in our clinical GBM tumor samples. We also confirmed that knockdown of HSPA7 might increase the efficiency of anti-PD1 therapy utilizing the GBO model, highlighting its potential as a novel target for immunotherapy.ConclusionsOur results indicated that HSPA7 could be a novel immunotherapy target for GBM patients.

Monitoring of the indicator Sustainable Development Goal (SDG) 11.3.1 is important for understanding the coordination between land consumption rate (LCR) and population growth rate (PGR). However, the spatiotemporal indicator SDG 11.3.1 changes at the urban agglomeration (UA) level, and the relationship between LCR and PGR in the prefecture-level cities from different UAs remains unclear. In this study, we monitored the spatiotemporal indicator SDG 11.3.1 in the Yangtze River Economic Belt (YREB) and its three major UAs (i.e., Chengdu–Chongqing (CC), the Middle Reaches of the Yangtze River (MRYR), and the Yangtze River Delta (YRD)) for the periods 2000–2010, 2010–2015, and 2015–2018, using the space–time interaction (STI) method and Pearson’s method. Our major findings were as follows: (1) Compared with the world average of 1.28 for LCRPGR (i.e., ratio of LCR to PGR), except for the LCRPGR of the YRD (2000–2018) and CC (2000–2010), the LCRPGR of CC, the MRYR, and the YREB was lower than 1.28 during 2000–2018. (2) The gaps in both population and built-up area between the YREB and the three UAs did not narrow, but widened. (3) Compared with the LCRPGR in China, except for the LCRPGR of the YRD (2000–2018) and CC (2000–2010), the LCRPGR of the YREB increased from 1.21 to 1.23 between 2000–2010 and 2010–2015, and then decreased to 1.16 in 2015–2018, indicating that the relationship between LCR and PGR in the YREB is relatively stable. (4) A significant positive relationship (p < 0.001) was found between LCR and PGR in CC, the MRYR, the YRD, and the YREB. We conclude that the indicator SDG 11.3.1 is a helpful tool for evaluating land-use efficiency caused by the LCR and PGR at the UA level. Our results provide information support for promoting sustainable and coordinative development between LCR and PGR.